Surgical Research Center, Université Paris Est-Créteil, Créteil, France.
J Thorac Cardiovasc Surg. 2013 Jun;145(6):1627-34. doi: 10.1016/j.jtcvs.2012.07.050. Epub 2012 Aug 27.
The singularity of the ascending aorta regarding mechanisms driving aneurysm formation requires the development of specific animal models. We investigated if adventitial elastase application results in ascending aorta aneurysms in rats.
Adult Lewis rats (n = 26) were anesthetized, their ascending aortas measured by transthoracic ultrasound, and exposed via median sternotomy. Elastase or saline was applied on the ascending aortic adventitia. Ascending aorta diameters were monitored by ultrasound at 10 and 30 days, when the animals were killed. Wall area was measured on orcein stained sections. Matrix metalloproteinase-2 and matrix metalloproteinase-9 levels were quantified on gelatin zymography.
Following elastase application, ascending aortic diameter increased at 10 and 30 days follow-up by 38% and 44%, respectively (P = .004). Despite thinning of the media secondary to vascular dilation, standardized medial area was not different between elastase-treated aortas and controls. Standardized total wall area had a significant increase in treated aortas compared with controls. Active matrix metalloproteinase-2 was significantly increased at 30 days in treated aortas, whereas active matrix metalloproteinase-9 was no different from controls.
Elastase application on rat ascending aortic adventitia produced aneurysms, creating a reproducible model. Aortic wall remodeling evolved toward an increase in total wall area, reproducing the main structural features of this disease in human beings.
升主动脉在驱动动脉瘤形成的机制方面具有独特性,这需要开发特定的动物模型。我们研究了在大鼠中应用外膜弹性蛋白酶是否会导致升主动脉瘤。
成年 Lewis 大鼠(n=26)被麻醉,通过经胸超声测量其升主动脉,并通过正中胸骨切开术暴露。弹性蛋白酶或生理盐水应用于升主动脉外膜。在 10 天和 30 天通过超声监测升主动脉直径,此时处死动物。在胭脂红染色切片上测量壁面积。明胶酶谱法定量基质金属蛋白酶-2 和基质金属蛋白酶-9 水平。
弹性蛋白酶应用后,升主动脉直径在 10 天和 30 天随访时分别增加了 38%和 44%(P=0.004)。尽管血管扩张导致中膜变薄,但弹性蛋白酶处理的主动脉与对照组的标准化中膜面积没有差异。与对照组相比,处理的主动脉标准化总壁面积显著增加。处理的主动脉中活性基质金属蛋白酶-2 在 30 天时显著增加,而活性基质金属蛋白酶-9 与对照组无差异。
弹性蛋白酶应用于大鼠升主动脉外膜可产生动脉瘤,从而创建了一个可重复的模型。主动脉壁重塑向总壁面积增加的方向发展,再现了人类这种疾病的主要结构特征。